scholarly journals Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction

Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 578-587 ◽  
Author(s):  
AD Schreiber ◽  
DB Cines ◽  
C Zmijewski ◽  
RW Colman
Keyword(s):  
Human Platelets ◽  
Metabolic Energy ◽  
Igg Antibody ◽  
Platelet Surface ◽  
Release Reaction ◽  
Platelet Release ◽  
High Concentrations ◽  
Antibody Levels ◽  
Pharmacologic Agents

Abstract We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement- mediated platelet alterations.

scholarly journals Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction

Blood ◽  
1979 ◽  
Vol 53 (4) ◽  
pp. 578-587
Author(s):  
AD Schreiber ◽  
DB Cines ◽  
C Zmijewski ◽  
RW Colman
Keyword(s):  
Human Platelets ◽  
Metabolic Energy ◽  
Igg Antibody ◽  
Platelet Surface ◽  
Release Reaction ◽  
Platelet Release ◽  
High Concentrations ◽  
Antibody Levels ◽  
Pharmacologic Agents

We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement- mediated platelet alterations.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

The Effect of the Phospholipase Inhibitor Mepacrine on Platelet Aggregation, the Platelet Release Reaction and Fibrinogen Binding to the Platelet Surface

1981 ◽  
Vol 45 (03) ◽  
pp. 257-262 ◽  
Author(s):  
P D Winocour ◽  
R L Kinlough-Rathbone ◽  
J F Mustard
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Surface ◽  
Release Reaction ◽  
Fibrinogen Binding ◽  
Platelet Release

SummaryWe have examined whether inhibition by mepacrine of freeing of arachidonic acid from platelet phospholipids inhibits platelet aggregation to collagen, thrombin or ADP, and the release reaction induced by thrombin or collagen. Loss of arachidonic acid was monitored by measuring the amount of 14 C freed from platelets prelabelled with 14 C-arachidonic acid. Mepacrine inhibited 14 C loss by more than 80% but did not inhibit thrombin-induced platelet aggregation and had a small effect on release. ADP-induced platelet aggregation did not cause 14 C loss. Mepacrine inhibited ADP-induced platelet aggregation by inhibiting the association of fibrinogen with platelets during aggregation. The effect of mepacrine on fibrinogen binding could be considerably decreased by washing the platelets but the inhibition of 14 C loss persisted. Platelets pretreated with mepacrine and then washed show restoration of aggregation to collagen. Thus, mepacrine has two effects; 1. it inhibits phospholipases, 2. it inhibits fibrinogen binding. Freeing of arachidonic acid is not necessary for platelet aggregation or the release reaction.

Inhibition by Phenol and Phenolic Acids of Platelet Release Reaction

1973 ◽  
Vol 30 (02) ◽  
pp. 334-338 ◽  
Author(s):  
Felisa C. Molinas
Keyword(s):  
Renal Failure ◽  
Phenolic Compounds ◽  
Phenolic Acids ◽  
Platelet Function ◽  
Deleterious Effect ◽  
Release Reaction ◽  
Contributory Factors ◽  
Adp Release ◽  
Platelet Release

SummaryIt has been postulated that the high phenol and phenolic acids plasmatic levels found in patients with chronic renal failure are contributory factors in the abnormal platelet function described in these patients. This hypothesis was corroborated by “in vitro” studies showing the deleterious effect of these compounds on certain platelet function after pre-incubation of PRP with phenol and phenolic compounds. The present studies were conducted to determine the influence of phenolic compounds on platelet release reaction. It was found that phenol inhibited from 62.5 to 100% the effect of the aggregating agents thrombin, adrenaline and ADP on platelet 5-HT-14C release. The phenolic acids p-, m-, and o-HPAA inhibited from 36.35 to 94.8% adrenaline and ADP-induced platelet 5-HT-14C release. Adrenaline-induced platelet ADP release was inhibited from 27.45 to 38.10% by the phenolic compounds. These findings confirm the hypothesis that phenolic compounds interfere with platelet function through the inhibition of the release reaction.

Release, Aggregation and Lysis of Human Platelets by Antilymphocyte Globulin and Antiplatelet Serum

1976 ◽  
Vol 36 (02) ◽  
pp. 411-423 ◽  
Author(s):  
Nicholas Lekas ◽  
J. C Rosenberg
Keyword(s):  
Platelet Aggregation ◽  
Gamma Globulin ◽  
Human Platelets ◽  
Plasma Medium ◽  
Release Reaction ◽  
Clinical Events ◽  
Thrombotic Complications ◽  
Platelet Release ◽  
Free Media

SummaryHuman platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.

scholarly journals Loss of 111Indium as indicator of platelet injury

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 350-353 ◽  
Author(s):  
JH Joist ◽  
RK Baker
Keyword(s):  
Small Molecules ◽  
Adenine Nucleotides ◽  
Human Platelets ◽  
Metabolic Energy ◽  
Platelet Factor ◽  
Platelet Protein ◽  
Threshold Rate ◽  
Immune Injury ◽  
Triton X

Abstract We previously demonstrated that platelets can be labeled with 111Inoxine with high labeling efficiency and that 111In is not liberated from labeled platelets during the platelet release reaction or prolonged in vitro storage. In view of these findings, we examined the potential usefulness of loss of 111In from labeled platelets as an indicator or platelet damage by comparing the loss of 111In with that of 51Cr and LDH (in some experiments also with platelet factor 3 availability) under different conditions of platelet injury. When washed human platelets labeled with either 51Cr-chromate or 111In-oxine were exposed to increasing concentrations of detergents (Triton X-100, lysolecithin), threshold, rate, and extent of loss of 111In, 51Cr and, LDH were similar. In contrast, when labeled platelets were depleted of metabolic energy by incubation in glucose-free Tyrode albumin solution or glucose-depleted plasma in the presence of antimycin A and 2-deoxy-D- glucose, loss of 51Cr (and PF3a) occurred earlier and progressed at a faster rate than that of 111In or LDH. Similar results were obtained when platelets were exposed to increasing concentrations of PlA1 antibody, causing complement-mediated immune injury. The findings indicate that with certain agents that cause rapid platelet disruption (lysis), different platelet constituents are lost at similar rates. However, under conditions of more subtle or slowly progressive platelet injury, small molecules such as adenine nucleotides (51Cr) may escape earlier and at faster rates than larger molecules such as LDH or 111In- binding platelet protein. Thus, neither 111In loss nor LDH loss appear to be suitable indicators for sublytic or prelytic platelet injury.

Impaired Platelet Function in Sept8-Deficient Mice In Vitro

2020 ◽  
Author(s):  
Kerstin Jurk ◽  
Katharina Neubauer ◽  
Victoria Petermann ◽  
Elena Kumm ◽  
Barbara Zieger
Keyword(s):  
Platelet Function ◽  
Thrombin Generation ◽  
Human Platelets ◽  
Platelet Surface ◽  
Integrin Αiibβ3 ◽  
Glycoprotein Vi ◽  
Fibrinogen Receptor ◽  
Static Conditions ◽  
The Impact

AbstractSeptins (Septs) are a widely expressed protein family of 13 mammalian members, recognized as a unique component of the cytoskeleton. In human platelets, we previously described that SEPT4 and SEPT8 are localized surrounding α-granules and move to the platelet surface after activation, indicating a possible role in platelet physiology. In this study, we investigated the impact of Sept8 on platelet function in vitro using Sept8-deficient mouse platelets. Deletion of Sept8 in mouse platelets caused a pronounced defect in activation of the fibrinogen receptor integrin αIIbβ3, α-granule exocytosis, and aggregation, especially in response to the glycoprotein VI agonist convulxin. In contrast, δ-granule and lysosome exocytosis of Sept8-deficient platelets was comparable to wild-type platelets. Sept8-deficient platelet binding to immobilized fibrinogen under static conditions was diminished and spreading delayed. The procoagulant activity of Sept8-deficient platelets was reduced in response to convulxin as determined by lactadherin binding. Also thrombin generation was decreased relative to controls. Thus, Sept8 is required for efficient integrin αIIbβ3 activation, α-granule release, platelet aggregation, and contributes to platelet-dependent thrombin generation. These results revealed Sept8 as a modulator of distinct platelet functions involved in primary and secondary hemostatic processes.

The Role of Bacteroides Gingivalis in Periodontal Disease

1988 ◽  
Vol 2 (2) ◽  
pp. 260-268 ◽  
Author(s):  
K. Okuda ◽  
I. Takazoe
Keyword(s):  
Surface Antigens ◽  
Biological Properties ◽  
Igg Antibody ◽  
Cotton Threads ◽  
Bacteroides Gingivalis ◽  
Antibody Levels ◽  
Mandibular First Molar ◽  
Attachment Factor

The microbial flora in adult advanced periodontitis lesions is comprised of Gram-negative rods, with Bacteroides gingivalis as one of the major representatives. This review deals with biological properties of surface antigens, hemagglutinin (attachment factor), and capsular structure of B. gingivalis. Sera containing high IgG antibody levels to B. gingivalis enhanced the complement-mediated bactericidal activity in vitro, although the susceptibility to complement-mediated lysis differed among B. gingivalis strains. The protective effect of immunization against B. gingival is infection was examined in hamsters in which cotton threads had been tied to the gingival margins of the mandibular first molar. Repeated oral topical application of hyper-immune sera against B. gingivalis resulted in effective elimination of the organisms from the periodontal lesions in the experimental animals.

Human Immunoglobulins for Intravenous Use: Comparison of Available Preparations for Group B Streptococcal Antibody Levels, Opsonic Activity, and Efficacy in Animal Models

PEDIATRICS ◽  
1990 ◽  
Vol 86 (6) ◽  
pp. 955-962
Author(s):  
Laurence B. Givner
Keyword(s):  
Animal Models ◽  
Neonatal Sepsis ◽  
Protective Efficacy ◽  
Group B Streptococcus ◽  
Igg Antibody ◽  
Opsonic Activity ◽  
Immunoglobulin Preparations ◽  
Group B ◽  
Antibody Levels

Currently available human immunoglobulin preparations for intravenous use (IVIGs) are being used (with antibiotics) by some physicians for therapy of sepsis in newborns. Most neonatal sepsis and/or meningitis in this country is caused by group B Streptococcus (GBS), and most of these cases are due to type III GBS (III-GBS). The killing of III-GBS in vitro is dependent on specific IgG antibody. Adequate serum levels of specific III-GBS antibody protect the exposed newborn from the development of invasive disease. Therefore, III-GBS was used as a model to evaluate the activity of three IVIG preparations available for clinical use. Specific antibody levels, in vitro opsonophagocytic killing, and protective efficacy in animal models revealed differences in activity for III-GBS between the three IVIG preparations as well as between IVIG lots from the same manufacturer. Furthermore, it was found that the effect of IVIG using one of the assay methods may not reliably predict activity obtained using the other assays. These data document the inability to predict functional activity against a specific pathogen such as GBS on the part of a lot of IVIG chosen at random. In view of these findings and of the limited data evaluating clinical efficacy, IVIG cannot be recommended at this time for use in the therapy of infectious diseases such as neonatal sepsis.

scholarly journals Calcium-dependent cysteine protease activity in the sera of patients with thrombotic thrombocytopenic purpura

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1683-1687 ◽  
Author(s):  
WG Murphy ◽  
JC Moore ◽  
JG Kelton
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Cysteine Protease ◽  
Platelet Activating Factor ◽  
Aminocaproic Acid ◽  
Human Platelets ◽  
Thrombocytopenic Purpura ◽  
Platelet Surface ◽  
Calcium Dependent

Abstract Plasma and serum from patients with thrombotic thrombocytopenic purpura (TTP) can cause activation and aggregation of normal human platelets in vitro. It is possible that this platelet-activating factor contributes to the disease. In this report we describe studies designed to identify the platelet-activating factor in TTP. Platelet activation by sera from 15 patients with TTP was inhibited by leupeptin, iodoacetamide, and antipain but not by phenylmethylsulphonylfluoride, epsilon-aminocaproic acid, soybean trypsin inhibitor, aprotinin, and D-phenylanyl-1-prolyl-1- arginine chloromethyl ketone. These studies suggested that the platelet- activating factor in TTP serum was a cysteine protease. We confirmed that a calcium-dependent cysteine protease (CDP) was present in the sera of each of the 15 patients when we used an assay based on the ability of CDP to proteolyse platelet membrane glycoprotein 1b (GP1b) and hence to abolish the ability of CDP-treated normal platelets to agglutinate in the presence of ristocetin and von Willebrand factor. This proteolytic activity was inhibited by EDTA, leupeptin, antipain, iodoacetamide, and by N-ethyl-maleamide (NEM) but not by the serine protease inhibitors. Activity was detected in 15 of 15 patients with TTP tested before therapy was begun. In contrast, no activity was detected in the serum of any of five of the TTP patients tested in remission or in any of the sera from 36 patients with thrombocytopenia and 423 nonthrombocytopenic controls. To look for in vivo CDP activity in patients with TTP, we studied platelets from two patients with acute TTP (drawn into acid-citrate-dextrose, NEM, and leupeptin). These platelets showed a loss of GP1b from the platelet surface. Both patients were also studied in remission: GP1b on the platelet surface had returned to normal. These studies provide evidence that CDP is present in the sera of patients with TTP, that it is specific to this disease, and that is is active in vivo as well as in vitro. We postulate that a disorder of CDP homeostasis plays a major role in the pathophysiology of TTP.

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